A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Phase 2

Completed

Conditions: Non-small Cell Lung Cancer (NSCLC)

Interventions: Drug: Durvalumab

Registration Number: NCT03693300

Lead Sponsor: AstraZeneca

Brief Summary: This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks \[q4w\] in participants with unresectable Stage III Non-Small Cell Lung Cancer (NSCLC), who have not progressed following platinum-based sequential chemoradiation therapy (sCRT). This study will be conducted in Europe and North America.

Detailed Description: This is a Phase II, open-label, multi-centre study to determine safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) monotherapy in participants with unresectable Stage III NSCLC who have not progressed following definitive, platinum-based sCRT. Approximately, 150 participants will be treated with the study drug in Europe and North America. Participants will be in complete response (CR), partial response (PR), or have stable disease (SD) following definitive, platinum-based sCRT, as assessed by the Investigator and further supported by the screening imaging radiological assessment. Participants must not have progressed following definitive, platinum-based sCRT; radiation therapy must be completed within 42 days prior to first Investigational product (IP) dose administration. Participants must have histologically- or cytologically-documented NSCLC and locally-advanced, unresectable Stage III disease. Participants will be treated with the study drug in 2 cohorts: approximately 100-120 participants in the World Health Organization/Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) 0 to 1 Cohort and up to 30 participants in the WHO/ECOG PS 2 Cohort.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 117

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
WHO/ECOG PS 0 to 1 Cohort	Durvalumab	100-120 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
WHO/ECOG PS 2 Cohort	Durvalumab	up to 30 participants will receive 1500 mg Durvalumab (MEDI4736) monotherapy via IV infusion q4w for up to a maximum of 24 months (up to 26 doses/cycles) with the last administration at Week 104. The study drug should be discontinued prior to 24 months if there is clinical progression or confirmed radiological progression or if there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Grade 3 and Grade 4 Treatment-related Adverse Events (TRAEs)	Up to 6 months	Safety and tolerability of Durvalumab as defined by Grade 3 and Grade 4 TRAEs following IV infusion administration was assessed.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	From the first date of treatment until the date of objective disease progression or death (approximately upto 48 months)	The efficacy of Durvalumab (MEDI4736) treatment in terms of PFS. PFS was defined as the time from the first date of treatment until the date of objective disease progression based on Investigator's assessment according to RECIST 1.1 or death (by any cause in the absence of progression) regardless of whether the patient withdraws from IP or receives another anticancer therapy prior to progression.
Percentage of Patients Progression-free at 12 Months	From the first date of treatment until the date of objective disease progression or death (upto 12 months)	The percentage of patients treated with Durvalumab who are progression-free was estimated. PFS12 according to RECIST 1.1 as assessed by the Investigator.
Overall Survival (OS)	From the first date of treatment until death due to any cause (approximately upto 48 months)	The efficacy of Durvalumab (MEDI4736) treatment in terms of OS were assessed. OS was defined as the time from the first date of treatment until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Objective Response Rate (ORR)	From 8 weeks ±1 week after investigational product (IP) treatment initiation and continue every 8 weeks (q8w) ±1 week through 52 weeks and every 12 weeks (q12w) ±1 week until disease progression (approximately upto 48 months)	The efficacy of Durvalumab (MEDI4736) treatment in terms of ORR were assessed. ORR (based on Investigator assessed response to treatment of complete response (CR) and partial response (PR) as per RECIST 1.1 criteria), together with the corresponding 95% CI, was reported for patients. Objective response is complete response (CR), or partial response (PR) confirmed by a follow-up visit at least 4 weeks after. Both visits contributing to response should have occurred before any further anti-cancer therapy, in order for the patient to be considered a responder. Responses that occurred after the start of subsequent anti-cancer therapy were not included in the numerator. Response excluded unconfirmed response. Participants with unconfirmed responses include those whose CR, or PR don't have a confirmed response. These responses occur at any time during the study, recur after anti-cancer therapy, and these participants were missing for a follow-up visit 4 weeks after.
Percentage of Patients Alive	From the first date of treatment until the date of objective disease progression or death (12 months, 24 months, and 36 months)	Percentage of patients alive at 12 months, 24 months, and 36 months were estimated.
Duration of Response (DOR) From Onset of Response	From 8 weeks ±1 week after IP treatment initiation and continue q8w ±1 week through 52 weeks and q12w ±1 week until disease progression (approximately upto 48 months)	The efficacy of Durvalumab (MEDI4736) treatment in terms of DoR were assessed. DoR was defined as the time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression. If a patient did not progress following a response, then the patients' DoR was censored at the PFS censoring time.
Lung Cancer Mortality	From date of treatment start until death due to lung cancer (approximately upto 48 months)	The efficacy of durvalumab (MEDI4736) treatment in terms of lung cancer mortality was assessed. Lung Cancer Mortality was defined as the time from the date of treatment start until death due to lung cancer. Any patient not known to have died due to lung cancer will be censored based on the last recorded date on which the patient was known to be alive or died due to reason other than lung cancer.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interests (AESIs), and Immune-mediated Adverse Event (imAEs)	Until the final visit (upto 48 months)	The safety and tolerability profile of Durvalumab(MEDI4736) treatment, including all AEs were assessed.